Some think that the song is in the musical continuum that stretches from 'talking blues' and similar songs of the early 20th Century to modern rap. There is also a rhythmical and lyrical similarity to the folk song "Shortnin' Bread".

The song's first line is a reference to codeine distillation and politics of the time: "Johnny's in the basement mixing up the medicine / I'm on the pavement thinkin' about the Government".[4] The song also depicts some of the growing conflicts between "straight" or "square" (40-hour workers) and the emerging 1960s counterculture. The widespread use of recreational drugs, and turmoil surrounding the Vietnam War were both starting to take hold of the nation, and Dylan's hyperkinetic lyrics were dense with up-to-the-minute allusions to important emerging elements in the 1960s youth culture. According to rock journalist Andy Gill, "an entire generation recognized the zeitgeist in the verbal whirlwind of 'Subterranean Homesick Blues'."[4]

The song also references the struggles surrounding the American civil rights movement ("Better stay away from those / That carry around a fire hose"). (During the civil rights movement, peaceful protestors were beaten and sprayed with high pressure fire hoses.) In spite of the political nature of the lyrics, the song went on to become the first Top 40 hit for Dylan in the United States.[5]

Listed by Rolling Stone magazine as the 332nd "Greatest Song of All Time",[6] "Subterranean Homesick Blues" has had a wide influence, resulting in iconic references by artists and non-artists alike. Most famously, its lyric "you don't need a weatherman to know which way the wind blows" was the inspiration for the name of the American radical left group the Weathermen, a breakaway from the Students for a Democratic Society.[7]John Lennon was reported to find the song so "captivating" that he didn't know how he'd be able to write a song that could "compete" with it.[8] The group Firehose (former Minutemen members) took its name from another of the song's enigmatic warnings: "Better stay away from those that carry around a fire hose..." In addition, the opening of the last verse,"Ah get born, keep warm", provided the Australian garage rock band Jet with the title of their debut album Get Born.

In the same way that Dylan paid homage to Jack Kerouac's novel, The Subterraneans,[9] "Subterranean Homesick Blues" has been referenced in the titles of various songs, for example, Radiohead's "Subterranean Homesick Alien" from 1997's OK Computer, the ska punk band Mustard Plug's "Suburban Homesick Blues" from 1997's Evildoers Beware,"300 M.P.H. Torrential Outpour Blues" by The White Stripes and the Memphis indie band The Grifters' "Subterranean Death Ride Blues", the B-side of a 1996 single. It was also the basis for the title of the second episode of Law & Order's premiere season, "Subterranean Homeboy Blues".

Echo & the Bunnymen's 1980 song, "Villiers Terrace," includes the line, "There's people rolling 'round on the carpet/Mixin' up the medicine."

The Gaslight Anthem's song "Angry Johnny and the Radio", from their 2007 album Sink or Swim, includes the lines "And I'm still here singin', thinking about the government" and "Are you hidin' in a basement, mixin' up the medicine?"

In addition to the song's influence on music, the song was used in what became one of the first "modern" promotional film clips, the forerunner of what later became known as the music video. Although Rolling Stone ranked it 7th in the magazine's October 1993 list of "100 Top Music Videos",[14] the original clip was actually the opening segment of D. A. Pennebaker's film, Dont Look Back, a documentary on Bob Dylan's 1965 tour of England. In the film, Dylan, who came up with the idea, holds up cue cards for the audience, with selected words and phrases from the lyrics. The cue cards were written by Donovan, Allen Ginsberg, Bob Neuwirth and Dylan himself.[4] While staring at the camera, he flips the cards as the song plays. There are intentional misspellings and puns throughout the clip: for instance, when the song's lyrics say "eleven dollar bills" the poster says "20 dollar bills". The clip was shot in an alley behind the Savoy Hotel in London where Ginsberg and Neuwirth make a cameo in the background. For use as a trailer, the following text was superimposed at the end of the clip while Dylan and Ginsberg are exiting the frame: "Surfacing Here Soon | Bob Dylan in | Don't Look Back by D. A. Pennebaker." Thanks to the back of the Savoy Hotel retaining much of the same exterior as in 1965 the alley used in the video sequence has been identified as the Savoy Steps [15].

In addition to the Savoy Hotel clip, two alternate promotional films were shot: one in a park where Dylan, Neuwirth and Ginsberg are joined by a fourth man[citation needed], and another shot on the roof of an unknown building (possibly the Savoy Hotel). A montage of the clips can be seen in the documentary No Direction Home.

The film clip was used in September 2010 in a promotional video to launch Google Instant[16]. As they are typed, the lyrics of the song generate search engine results pages (SERPS).

"Weird Al" Yankovic used the concept twice: first, for his 1989 song "UHF" (though in this case he was in fact parodying the INXS version) and second, for the song "Bob" from his 2003 album Poodle Hat. In "Bob", the lyrics are all palindromes, and the video depicts Yankovic dressed as Dylan dropping cue cards with each palindrome.[17]

The 1992 Tim Robbins film Bob Roberts features Robbins in the title role as a right-wing folk singer who uses Dylan's cue-card concept for the song "Wall Street Rap".[18]

French singer Alain Chamfort commissioned director Bruno Decharme to make an exact replica of the original video for his song "Les yeux de Laure".[19]

Filk performer The great Luke Ski recorded two Star Wars-themed parodies of "Subterranean Homesick Blues": "Star Wars Trilogy Homesick Blues", about the Original Trilogy, and "Star Wars Prequel Homesick Blues", about the Prequel Trilogy. He also filmed a video for the former, with Ski dressed as Dylan dropping cue cards as in the "Subterranean" clip.[20]

Richard Curtis's film Love Actually has a character tell another that he is in love with her, by holding up cards with messages on them.

The video for "Misfit" by Curiosity Killed the Cat features Andy Warhol standing motionless in an alleyway, dropping cue cards that are blank, while the band's singer energetically dances to the left of him.

Directorial duo Greifer & Krötenbluth shot a promo for the German band Wir sind Helden's 2005 single "Nur ein Wort", in which the group's singer and guitarist use cue cards and other effects.[22]

Scottish band Belle and Sebastian pay homage to the Subterranean Homesick Blues film in the music video for the song "Like Dylan in the Movies" on the album If You're Feeling Sinister. The video was filmed and edited by band members, and was not released until the 2003 documentary/video compilation Fans Only. Part of the song lyrics are a play on the title of the Dylan documentary: "If they follow you, don't look back, like Dylan in the movies."

The American punk band Anti-Flag used the concept in the clip for their song "Turncoat".

Pop-punk band The Matches created a video for their song, "Salty Eyes", using televisions as opposed to flashcards - throwing them around and dropping the televisions as the lyrics are said. Also, in tribute to the clip, one television says "Clean Nose", which when the camera pans back around, shows lead singer Shawn Harris drawing white over letters and changing them to say "However Naive", one of the Salty Eyes' Lyrics.

Argentinian singer/songwriter León Gieco paid homage to Dylan by using cue cards in his video clip for the song El ídolo de los Quemados, in his 2001 album, Bandidos Rurales.

Steve Earle implements the technique as part of the video for his 2002 single, Jerusalem.

Convention producers The Madow Brothers did a scene using the card-dropping theme which was shot in a Las Vegas alleyway for the opening video to TBSE 2007.

Joan O'Connor, RN, produced "Just Say No to Big Tobacco Co." in 2008, a music video of a song written and performed by her. The video was a collaborative project with her 'Smoking Reduction and Cessation Group for People Living with Mental Illnesses.' [25].

In an early episode of the Nickelodeon show The Adventures of Pete and Pete, entitled "Don't Tread on Pete," Big Pete, while talking about cafeteria food and the different names for a salisbury steak, is shown in black and white dressed as Dylan and holding up cue cards with the different names.

In late 2008, ESPN personality Kenny Mayne used a similar video to promote Mayne Street, a Web-only series on ESPN.com in which he stars.

In 2008, rapper Evidence shot a music video for his single "The Far Left" as a tribute to Subterranean Homesick Blues. The video also includes him holding words to the song and drawn pictures as well.

In the 2008 documentary "Gold and Silver and Sunshine - The Making of Dig Out Your Soul", the English band Oasis introduced each point of interest using the card-dropping theme from the Subterranean Homesick Blues video.

Singer-songwriter, Julian Velard, pays tribute to Dylan using the card-dropping motif on the intro page to his website.[26]

A 2009 Fruit of the Loom commercial uses a similar tune with the fruit characters walking down a school hallway. Instead of cards, the actual items referred to in the song are held up and dropped.

In 2010 phrase "in the basement mixing up the medicine" and "sitting on the pavement thinking about the government" is used in Yelawolf's song "mixing up the medicine" featuring Juelz Santana on Yelawolf's "Trunk Muzik" album